Process of producing sulphonyl halides



Patented Oct. 3, 1939 UNITED STATES PATENT OFFICE 2,174,853 PROCESS OF PRODUCING SULPHONYL HALIDES Treat B. Johnson, Be

Rohm & Haas Company, Phllad thany, Conn.

assignmto elphia, Pa.. a

corporation of Delaware No Drawing. Application A Serial No. 201.72

9 Claims. This invention relates to an improved process for the production 01' suiphonyl halides. The

phoe- In my copending appications, Serial Nos. 72,-

983, filed April 6, 1936, now Patent No. 2,146,744;

45 136,129, filed April 10, 1937,

direc y.

0 compounds, The reactions appar- From the sulphonyl halide organic thiocyanates to the corresponding suiphonyl halides, the thiocyanate is simply suspended or dissolved in water, and subjected to the action of a halogen, as by stirring the solution or suspension in an atmosphere of gaseous chlorine or bromine, by bubbling chlorine or bromine through the solution or suspension. or by otherwise bringing a halogen into contact with the aqueous suspension or solution, as by dripping bromine into the solution or suspension. If the thiocyanate is insoluble in water, or relatively insoluble in water, a small quantity of an emulsifying or dispersing agent may be added to promote the dispersion of the thincyanate, but the use of such dispersing agent is, of course, unnecessary. Also, if desired, an inert organic solvent for the thiocyanate may be added.

In general, the temperature of mixture should be kept relatively tageously between about and 30 suits are usually obtained between 0 15 C.

The reaction, with most organic thiocyanates, proceeds rapidly and smoothly. The yields are generally excellent, and in many cases quantitative. The alkyl, aralkyl and allcyclic thlocyanates react more readily and rapidly than do the aryl thiocyanates, such as the phenyl thiocyananates. With the alkyl, aralkyl and allcyclic thiocyanates, the reaction is generally completed in a few hours, whereas it may take a considerably longer period of time to complete the reaction with aryl thiocyanates, such as the phenyl thiocyanates. the sulphonyl halide corresponding to the halogen used for effecting the reaction is formed directly, and generally separates in an oily layer. The sulphonyl halides may be purified by dissolving in ether or other organic solvents, with drying in the usual manner over anhydrous sodium sulphate or other water absorbing agents, or in other ways. of the lower alkyl sulphonyl halides, such as methyl, ethyl, butyl sulphonyl chloride, may be distilled without decomposition, using a reduced pressure. The higher alkyl sulphonyl chlorides, the alicyclic or unsaturated alkyl sulphonyl chlorides, and the sulphonyl bromides are advantageously purified by converthe reaction low, advan- C. Best re- C. and

by boiling with fluoride solution. The

or crystallized from appropriate solvents for purification. Similarly, the sulphonyl halides are readily converted into corresponding sulphonamids, as by treatment with ammonia or amines, such as aniline, etc. In general, these sulphonamids are stable, crystalline compounds which are readily purified by the usual methods of recrystallization from solvents.

The invention will be further illustrated by the following examples, although it is not limited thereto (parts by weight):

Example 1.-l2.46 parts of methyl thlocyanate and 100 parts of water are mixed in a vessel surrounded by an ice-water bath. The mixture is agitated vigorously while chlorine gas is passed into the mixture at a rate such that the temperature is maintained at C. or lower. The passage of the chlorine is continued until the yellow color of the reaction mixture shows that an excess of chlorine is present. This takes about one to two hours. The oil which separates is extracted with ether, and the resulting ether solution is washed first with sodium bisulphite solution and then with sodium bicarbonate soanhydrous calcium chloride. The methyl sulphonyl chloride is distilled t reduced pressure. It boils at 55 C.,/ll mm. It is readily converted to the corresponding sulphonlc acid by aqueous hydrolysis, and to the corresponding methyl sulphonamid by treatment with ammonia.

Example 2.-20 parts or ethyl thiocyanate suspended in 200 parts of water are agitated vigorously and kept at 0 to 5 C. while chlorine gas is introduced at the rate of 2 to 3 liters per hour. The introduction of the chlorine gas is continued until the reaction mixture has a permanent yellow color, indicating an excess of chlorine. The excess chlorine is removed by blowing air through the reaction mixture. The mixture is then. extracted with ether and the ether solution is washed with sodium bicarbonate and sodium thiosulphate solution, after which it is dried over anhydrous calcium chloride and distilled. Ethyl sulphonyl chloride, boiling at ll-72 C./20

gaseous chlorine is introduced, of the mixture being kept between After completion of the reaction, the n-propyl sulphonyl chloride is separated and purified as 1. It boils at 69 C./1l mm.

4.- parts of freshly crystallized, finely pulverized benzyl thiocyanate are suspended in 200 parts of water and the suspension is agitated vigorously while passing chlorine gas into the mixture. The temperature is maintained at 0 to 2 C. by means of a cooling mixture around the reaction vessel. when the formation of chlorine hydrate in the reaction vessel indicates the presence of an excess of chlorine, the cooling bath is removed and the temperature of the reaction mixture is allowed to rise slowly to room temperature while the introduction of the chlorine gas is continued. The benzyl sulphonyl chloride obtained may be filtered out of the reaction mixture as a slightly impure waxy solid melting at 84-38 C.

Example .-5 parts of freshly crystallized, finely pulverized p-nltro benzyl thiocyanate are ground into a thin paste with 100 parts of water. Chlorine gas is passed into the resulting suspension with vigorous stirring while maintaining the temperature at 4 to 5 C. for thirty minutes, after which the temperature of the reaction mixture is raised to room temperature and the introduction of chlorine is continued for four hours. The crude p-nitro benzyl sulphonyl chloride is separated. Aiter washing with ether and recrystallizing from benzene, a product melting at 9l-92 C. is obtained.

Example 6.-10 parts of phenyl thiocyanate are suspended chlorine is introduced into the resulting mixture for eight hours. An oil separates which may be distilled. Analysis of the distillate shows that the product contains less than half of the amount of combined chlorine required ior phenyl sulphonyl chloride, indicating that the reaction is incomplete. Chlorination under the same conditions for sixty hours yields a product which still contains some unchanged starting material. Nevertheless, the product obtained after eight hours of chlorination, as well as that alter sixty hours of chloriniii ation, contains phenyl sulphonyl chloride, as shown by the fact that the crude oily product forms phenyl sulphonyl anilide with aniline. As

pointed out above, the aryl thiocyanates do not react as readily with the halogen to form the corresponding sulphonyl halides as do the alkyl, alicyclic and araikyl thiocyanates.

Example 7.1l5 parts of n-butyl thiocyanate are stirred violently in 1500 parts of water in an atmosphere of chlorine. is maintained at a temperature of about to C. After about five hours, the absorption of chlorine ceases, and the oil layer, containing crude n-butyl sulphonyl chloride, is separated from the aqueous layer, washed with water and distilled under a vacuum. The redistilled n-butyl sulphonyl chloride boils at about 90 C./14 mm.

Example 8.--75 parts of Z-thiocyano-octane are violently agitated with 300 parts of water in an atmosphere of gaseous chlorine. The temperature of the reaction mixture is maintained at about 10 to about 20 C. by external cooling. The crude sulphonyl chloride formed separates as a heavy oil. It is washed with water and sodium bisulphite solution, and is then converted to octane- 2-sulphonyl fluoride by boiling with an excess of aqueous potassium fluoride. The resulting fluoride is a colorles oil boiling at about 88 C./3 mm.

Example 9. 4O parts of cyclopentyl thiocyanate are dispersed in 500 parts of water and the dispersion is violently agitated in an atmosphere of gaseous chlorine until the absorption of chlorine ceases. This requires about flve hours. The resulting cyclopentyl sulphonyl chloride separates as a heavy oil which is converted to the corresponding fluoride as in the preceding example. The fluoride is a colorless liquid boiling at about 60 C./3 mm.

Example 10.-- parts of cetyl thiocyanate are suspended in 700 parts of water and subjected to the action of chlorine at a temperature of 15 to 20 C. as in the preceding example. The cetyl sulphonyl chloride separates as a white greasy solid. It is cooled and separated by suction filtration as a white, waxy mass. This is purified by washing with water and sodium bisulphite. On boiling with aqueous potassium hydroxide, it forms cetyl potassium sulphonate.

Example 11.- 72 parts of crystalline 1,2-dithiocyano-ethane are suspended in 300 parts of water and subjected to the action of chlorine as in the preceding example while the temperature is maintained at 15 to 20 C. Ethane-1,2-disulphonyl chloride separates as a greasy white solid which may be separated by filtration from the solution.

Example 12.-- parts of p-ter-octyl phenoxyethyl thiocyanate are suspended in 300 parts of water and subjected to the action of chlorine as in the preceding example for three hours at 15 C. p-ter-octyl phenoxyethyl sulphonyl chloride separates as a thick oil which on boiling with excess caustic soda solution dissolves with the formation of p-ter-octyl phenoxyethyl sodium sulphonate, which yields a soapy aqueous solution.

Example 13.35 parts of cyclohexyl thiocyanate, suspended in 300 parts of water, are sub jected to the action of chlorine as in the preceding example while maintaining the temperature at 10 to, 15 C. Cyclohexyl sulphonyl chloride separates as a heavy oil which may be converted to cyclohexyl sulphonyl fluoride by boiling with aqueous potassium fluoride. The cyclohexyl sulphonyl fluoride boils at to 97 C./3 mm.

The reaction mixture Example 14.-100 parts of n-butoxyethoxyethyl thiocyanate are agitated with 750 parts or water. 240 parts of bromine are added dropwise to the mixture while maintaining the temperature at 10 C. The reaction mixture is agitated for about flve hours at about 5 to 10 C. after all of the bromine is added. The reaction mixture is then washed with cold water and-cold sodium blsuiphite solution while maintaining the temperature below about 10 C. n-butoxyethoxyethyl sulphonyl bromide forms as a heavy oil, which is converted to the more stable fluoride by aqueous potassium fluoride. The fluoride is a colorless. almost odorless oil, boiling at -120" C./3 mm.

Example 15.-Tetrahydroiuriuryl thiocyanate is converted to tetrahydroiurfuryl sulphonyl chloride as in Example 13. The sulphonyl chloride has a boiling point of about ll5-1l6 C. at 5 mm. pressure.

It will be understood that in the preceding examples, the reaction has been descibed as applied to a number of typical organic thlocyanates, with the production of the corresponding sulphonyl halides. These sulphonyl halides are readily converted to the sulphonic acids by aqueous hydrolysis. as by boiling with water or dilute acid, to the corresponding salts either by neutralization of the sulphonic acids or by boiling the halides with caustic solution, to corresponding sulphonamids by treatment with ammonia or amines, etc. These latter reactions have not been described in detail, as they are well known to chemists.

The new reaction of the present application is a general reaction applicable to organic thiocyanates generally, whether the carbon compound nucleus linked to the sulphur of the thiocyanate group is substituted or unsubstituted, and whether it is alkyl, aralkyl, aryl, alicyclic or heterocyclic in nature. Among the alkyl sulphonyl halides which may be readily produced by this method are the lower alkyl compounds, such as the methyl. ethyl, the isomeric propyls,- butyis, amyls, hexyls. heptyls, etc., as well as the higher alkyl sulphonyl halides, such as the cetyl, oleyl, stearyl, etc. Also, the various aralkyl sulphonyl halides are readily prepared, as well as the aryl, the alicyclic, and the heterocycllc sulphonyl halides. Among the sulphonyl halides which are readily prepared by the process of the present application are those corresponding to the following thiocyanates: methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, cetyl, oleyl, stearyl, palmityl, lauryl, benzyl, phenylethyl, nitrobenzyi, phenyl, tolyl, cyclopentyl, cyclohexyl, cyclopropyl, naphthyl, propylnaphthyl, tetrahydrofuriuiyl, B- acetoxyethyl, allyl, crotyl, citronnelyl, nitrotolyl, B-B-dlthiocyanoalkoxy ethers, thiocyanoethyl ether, B-B'-dithiocyano-alkyl ethers, diphenyl, diphenyl oxide, aminophenyl, aminotolyl, and others. These thiocyanates, and many others which may be used for the production of sulphony] halides in accordance with the present invention, are more or less readily prepared by known processes. The preparation of the thiocyanates is not a part of this invention.

It will be understood that the sulphonyl halides prepared as described may be converted into sulphonic acids, salts oi sulphonic acids. sulphonamids, etc, by known reactions, either after purifiestion, simple separation from the reaction mixture without purification, or by the treatment of the crude reaction products. In such cases, the crude sulphonyl derivative produced by reaction of an organic thiocyanate with a halogen is 75 somewliat unstable, and cannot be conveniently puriiied. In such cases it is irequently advantageous. ii purification is desired. to convert the product to a more stable or more easily purified 5 product. for purification or use. For example.

some of the sulphonyl bromides are quite unstable, and it is frequently advantageous to convert them to the more stable and more easily purified sulphonyl fluorides or sulphonamids.

I claim:

1. The process 0! sulphonyl halides which comprises subjecting an organic thiocyanate in which the nucleus 0! a carbon compound is linked through a carbon atom tothe sulphur of the thiocyanate radical to the action of a halogen in the presence 0! water.

2. The process of producing sulphonyl halides .which comprises subjecting an organic thiocyanate having an organic radical linked through a carbon atom to the sulphur of the thiocyanate radical to the action of a halogen in the presence of water.

3. The process of producing aliwl sulphonyl halides which comprises reacting an alkyl thic- 9,5 cyanate with a halogen in the presence of water.

Patent No. 2,17l 856.

TREAT B.

armese 4. The process oi producing aralkyl sulphonyl halides which comprises reacting an aralkyl thiccyanate with a halogen in the presence of water.

5. The process oi producing aryl sulphonyl halides which comprises reacting an aryl thiccyanate with a halogen in the presence of water.

6. The-process of producing sulphonyl halides which comprises reacting a compound of the formula RSCN, in which R is the nucleus of an organic compound linked through a carbon atom to the sulphur atom, with a halogen in the presence of water.

7. The process oi preparing sulphonyl halides which comprises reacting an organic thiocyanate with a halogen in the presence of water while maintaining the temperature below about 30 C.

- 8. The process of preparing sulphonyl halides which comprises reacting an organic thiocyanate with a halogen in the presence of water while maintaining the temperature between about 5 C. and about 15 C.

9. The process as in claim 1, in which the halogen used is chlorine.

TREAT B. JOHNSON.

CERTIFICATE OF CORRECTION.

October 5, 1959.

JOHNSON.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Pagel second column, line 55, for "react-ions" read reaction; page 2, second co lumn line 55, Example 5, for "11 mm." read 10 mm.; page 5, second column, line 75, for "such" read some} and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 7th day of November, A. D. 1959.

(Seal) Henry Van Arsdale Acting Commissioner of Patentssomewliat unstable, and cannot be conveniently puriiied. In such cases it is irequently advantageous. ii purification is desired. to convert the product to a more stable or more easily purified 5 product. for purification or use. For example.

some of the sulphonyl bromides are quite unstable, and it is frequently advantageous to convert them to the more stable and more easily purified sulphonyl fluorides or sulphonamids.

I claim:

1. The process 0! sulphonyl halides which comprises subjecting an organic thiocyanate in which the nucleus 0! a carbon compound is linked through a carbon atom tothe sulphur of the thiocyanate radical to the action of a halogen in the presence 0! water.

2. The process of producing sulphonyl halides .which comprises subjecting an organic thiocyanate having an organic radical linked through a carbon atom to the sulphur of the thiocyanate radical to the action of a halogen in the presence of water.

3. The process of producing aliwl sulphonyl halides which comprises reacting an alkyl thic- 9,5 cyanate with a halogen in the presence of water.

Patent No. 2,17l 856.

TREAT B.

armese 4. The process oi producing aralkyl sulphonyl halides which comprises reacting an aralkyl thiccyanate with a halogen in the presence of water.

5. The process oi producing aryl sulphonyl halides which comprises reacting an aryl thiccyanate with a halogen in the presence of water.

6. The-process of producing sulphonyl halides which comprises reacting a compound of the formula RSCN, in which R is the nucleus of an organic compound linked through a carbon atom to the sulphur atom, with a halogen in the presence of water.

7. The process oi preparing sulphonyl halides which comprises reacting an organic thiocyanate with a halogen in the presence of water while maintaining the temperature below about 30 C.

- 8. The process of preparing sulphonyl halides which comprises reacting an organic thiocyanate with a halogen in the presence of water while maintaining the temperature between about 5 C. and about 15 C.

9. The process as in claim 1, in which the halogen used is chlorine.

TREAT B. JOHNSON.

CERTIFICATE OF CORRECTION.

October 5, 1959.

JOHNSON.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows: Pagel second column, line 55, for "react-ions" read reaction; page 2, second co lumn line 55, Example 5, for "11 mm." read 10 mm.; page 5, second column, line 75, for "such" read some} and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 7th day of November, A. D. 1959.

(Seal) Henry Van Arsdale Acting Commissioner of Patents- 

